Oral Selinexor as Maintenance Therapy After First-Line Chemotherapy for Advanced or Recurrent Endometrial Cancer
Authors: Ignace Vergote, Jose Alejandro Pérez-Fidalgo, Erika Paige Hamilton, Giorgio Valabrega, Toon Van Gorp, Jalid Sehouli, David Cibula, Tally Levy, Stephen Welch, Debra L. Richardson, Eva M. Guerra, Giovanni Scambia, Stéphanie Henry, Pauline Wimberger, David S. Miller, Jaroslav Klat, Jerónimo Martínez-Garcia, Francesco Raspagliesi, Bhavana Pothuri, Ignacio Romero, Alice Bergamini, Brian Slomovitz, Fabienne Schochter, Estrid Høgdall, Lorena Fariñas-Madrid, Bradley J. Monk, Dayana Michel, Michael G. Kauffman, Sharon Shacham, Mansoor Raza Mirza, Vicky Makker, Ignace Vergote, Toon Van Gorp, Isabelle Cadron, Annelore Barbeaux, Nathalie Cornez, Stephanie Henry, Joseph Kerger, Debbie Debaere, Hannelore Denys, Mansoor Raza Mirza, Amit Oza, Lucy Gilbert, Stephen Welch, Michael Kolinsky, Qi Zhou, Jing Wang, Yingjie Yang, Kaijia Tu, Li Wang, Danbo Wang, Ge Lou, Xiaojian Yan, Jiaxin Yang, David Cibula, Jaroslav Klat, Bohuslav Melichar, Michal Zikan, Klaudia Reginacova, Vit Weinberger, Jalid Sehouli, Pauline Wimberger, Dirk Bauerschlag, Fabian Trillsch, Oliver Tome, Fabienne Schochter, Marco Battista, Bahriye Aktas, Kristina Luebbe, Mustafa Deryal, George Fountzilas, Athina Christopoulou, Christos Papadimitriou, Flora Zagouri, Limor Helpman, Tamar Safra, Tally Levy, Ilan Bruchim, Ora Rosengarten, Aviad Zick, Giorgio Valabrega, Giovanni Scambia, Giorgia Mangili, Francesco Raspagliesi, Carmela Pisano, Donata Sartori, Ugo de Giorgi, Jose Alejandro Perez-Fidalgo, Cesar Gomez-Raposo, Ignacio Romero, Maria Iglesias, Ana Santaballa, Nerea Ancizar, Purificación Estévez, Constanza Maximiano, Alfonso Yubero, Ana Oaknin, Eva Guerra, Lydia Gaba, Jeronimo Martinez, Emma Dotor, Vicky Makker, Debra Richardson, Jonathan Berek, Hye Sook Chon, Joseph Buscema, Meaghan Tenney, David Miller, Gregory Sutton, Daniel Spitz, Kristopher LyBarger, Erika Hamilton, Gregory Gilmore, Merrill Shum, Harshad Amin, Leslie Randall, Bhavana Pothuri, Katina Robison, Jonathan Boone, Joyce Barlin, Sharad Ghamande, Alfred Guirguis, Sudarshan Sharma, Iwona Podzielinski, Lisa Landrum, Nicole Nevadunsky, Amanda Jackson, Eirwen Miller, Radhika Gogoi, Bradley Monk, Restituto Tibayan, Noelle Cloven, Joseph de la Garza, Christine Lee, Carolyn Mathews, Anna Priebe, Michael Teneriello, Charles Anderson, Bhavana Pothuri, Fabio Cappuccini, David Miller, Michael G. Kaufman, Sharon Shacham, Yosef Landesman, Christopher J. Walker, Xulong Wang, Feng Wang, Changting Meng, Dayana Michel, Patricia Judson, Reshma Rangwala
Journal: Journal of Clinical Oncology (2023)

PURPOSE Selinexor inhibits exportin-1 (XPO1) resulting in nuclear accumulation of tumor suppressor proteins including p53 and has clinical activity in endometrial cancer (EC). The primary end point was to assess progression-free survival (PFS) with once-weekly oral selinexor in patients with advanced or recurrent EC. PATIENTS AND METHODS ENGOT-EN5/GOG-3055/SIENDO was a randomized, prospective, multicenter, double-blind, placebo-controlled, phase III study at 107 sites in 10 countries. Patients 18 years or older with histologically confirmed EC were enrolled. All had completed a single line of at least 12 weeks of taxane-platinum combination chemotherapy and achieved partial or complete response. Patients were assigned to receive 80 mg oral selinexor once weekly or placebo with 2:1 random assignment (ClinicalTrials.gov identifier: NCT03555422 ). RESULTS Between January 2018 and December 2021, 263 patients were randomly assigned, with 174 allocated to selinexor and 89 to placebo. The median PFS was 5.7 months (95% CI, 3.81 to 9.20) with selinexor versus 3.8 months (95% CI, 3.68 to 7.39) with placebo (hazard ratio [HR], 0.76 [95% CI, 0.54 to 1.08]; two-sided P = .126), which did not meet the criteria for statistical significance in the intent-to-treat population. Incorrect chemotherapy response stratification data for 7 (2.7%) patients were identified. In a prespecified exploratory analysis of PFS in audited stratification data, PFS for selinexor met the threshold for statistical significance (HR, 0.71; 95% CI, 0.499 to 0.996; two-sided P = .049). Furthermore, patients with the TP53 wild-type (wt) EC had a median PFS of 13.7 and 3.7 months with selinexor and placebo. The most common grade 3 treatment-related adverse events were nausea (9%), neutropenia (9%), and thrombocytopenia (7%). CONCLUSION The significance level for PFS was only met in the audited analysis. However, a preliminary analysis of a prespecified exploratory subgroup of patients with TP53wt EC showed promising results with selinexor maintenance therapy.